Osteoporosis in men is an important clinical problem, associated with significant morbidity, mortality and societal expense. Odanacatib (ODN), a selective oral inhibitor of cathepsin K, is currently being investigated as a treatment for osteoporosis. This Phase III, double-blind, randomised, placebo-controlled, 24-month study investigated the safety and efficacy of ODN for the treatment of men with osteoporosis. Eligible patients were men 4095 years of age with idiopathic osteoporosis or osteoporosis due to hypogonadism, who had a lumbar spine (LS), femoral neck (FN), or total hip (TH) T-score of ≤2.5 to ≧4.0 without prior vertebral fracture, or ≤1.5 to ≧4.0 with one prior vertebral fracture. Participants were randomised (1:1) to ODN 50 mg weekly or placebo. All received vitamin D (5600 IU/week) and calcium up to 1200 mg/day, if required. The primary efficacy outcome measure was the percent change from baseline in LS BMD. Secondary outcomes included changes in BMD at the FN, TH, and trochanter, bone turnover markers, and safety and tolerability. In total, 292 men were randomised and treated (mean age 68.8 years; 5.8% total testosterone levels <250 ng/dL). Compared with placebo, treatment with ODN for 24 months increased BMD at the LS and all 3 hip sites (TH, FN and trochanter) by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (LS, TH, and trochanter p<0.001; FN p=0.008) and decreased the bone resorption marker u-NTx/Cr (68%, p<0.001). Bone formation markers initially decreased with ODN, then returned towards levels found with placebo by Month 24. ODN was associated with an incidence of adverse events similar to placebo. In this study in men with osteoporosis, ODN increased spine and hip BMD, and decreased bone resorption with a smaller effect on bone formation. ODN is a promising potential therapy for the treatment of osteoporosis in men. (ClinicalTrials.gov number NCT01120600.)
Disclosure: EO and NB have received research grants and consulting fees from Merck. SA has received consulting fees from Merck. RC has received research grants from Merck. BL has received rewards/research grants and consulting fees, and participated in speakers bureaux for Merck. SD, HG, BBS, and ACS are employees of Merck. This study was sponsored by Merck & Co., Inc.